TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION

TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION

Bibliographic Details
Main Author: Mbimba, Thomas S., Jr
Language:English
Published: Kent State University / OhioLINK 2015
Subjects:
Biomedical Research
Cellular Biology
Molecular Biology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-kent14488415942021-08-03T06:33:56Z TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION Mbimba, Thomas S., Jr Biomedical Research Cellular Biology Molecular Biology In the present studies, we sought to understand the regulatory function of Trafficking protein particle complex 9 (TRAPPC9) in both osteoblast and osteoclast using in vivo and in vitro approaches. Furthermore, we wanted to determine the signal mechanism responsible for TRAPPC9-mediated function in bone cells. To that end, we utilized a loss of and gain of function approaches using the lentiviral vector system to downregulate or over-express TRAPPC9, respectively. Lastly, we evaluated the role of TRAPPC9 in two in vivo models using critical size defect for bone regeneration to evaluate osteoblast function and a calvaria osteolysis model for bone resorption to evaluate osteoclast function. Our overall premise is that TRAPPC9 is a negative regulator of osteoblast differentiation and its down-regulation enhances osteoblast differentiation and function on the other, hand TRAPPC9 is a positive regulator of osteoclast differentiation and function and its expression enhances osteoclast mediated bone resorption. Our results show that TRAPPC9 inhibition greatly enhances osteoblast differentiation and function in both Mesenchymal stem cells and osteoblast like MC3T3-E1 cell line in vivo and in vivo examination also showed an enhanced bone regeneration properties in animal treated with TRAPPC9 shRNA lentivirus. This inhibition was mediated through the activation of NF-¿B. Result also showed that TRAPPC9 inhibition showed suppressed cell proliferation by inhibiting cell cycle progression in both cell types. In osteoclast however, TRAPPC9 inhibition showed opposite effects; TRAPPC9 over-expression enhanced RANKL-induced osteoclast differentiation and function in vitro. In vivo experiment also showed that calvaries treated with lentiviral particles overexpressing TRAPPC9 enhanced RANKL-induced calvaria osteolysis. This inhibition was also mediated through the inhibition of NF-¿B activation. These data suggest that TRAPPC9 expression is important for both osteoblast and osteoclast differentiation and function. Our data also suggest that TRAPPC9 could be a potential target for therapeutic treatment of bone loss and improved fracture recovery. 2015-12-02 English text Kent State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594 http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.
collection NDLTD
language English
sources NDLTD
topic Biomedical Research
Cellular Biology
Molecular Biology
spellingShingle Biomedical Research
Cellular Biology
Molecular Biology
Mbimba, Thomas S., Jr
TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION
author Mbimba, Thomas S., Jr
author_facet Mbimba, Thomas S., Jr
author_sort Mbimba, Thomas S., Jr
title TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION
title_short TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION
title_full TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION
title_fullStr TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION
title_full_unstemmed TRAFICKING PROTEIN PARTICLE COMPLEX (TRAPPC) -9:A NOVEL PROTEIN REGULATOR OF NF-kB MEDIATED BONE FORMATION AND RESORPTION
title_sort traficking protein particle complex (trappc) -9:a novel protein regulator of nf-kb mediated bone formation and resorption
publisher Kent State University / OhioLINK
publishDate 2015
url http://rave.ohiolink.edu/etdc/view?acc_num=kent1448841594
work_keys_str_mv AT mbimbathomassjr trafickingproteinparticlecomplextrappc9anovelproteinregulatorofnfkbmediatedboneformationandresorption
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